Because of recent progress in the blood transfusion medical science, blood component transfusion that transfuses only components necessary for a recipient is mainly employed in the present blood transfusion medical treatment. Advantages such as a relieved burden on a recipient and an increased curing effect are given as the reasons for wide acceptance of the blood component transfusion. Blood component products, which are used for the transfusion, such as a concentrated erythrocyte product, concentrated platelet product, and blood plasma product, are prepared by centrifuging a whole blood product obtained by blood donation. A large amount of leukocytes is contained in blood products prepared in this manner. It has been discovered that such contained leukocytes induce comparatively slight side effects, such as headache, nausea, chills, and an non-hemolytic febrile transfusion reaction, as well as serious side effects, such as alloantigen sensitization, virus infection, and post-blood transfusion GVHD that seriously affect a recipient. For this reason, leukocyte-removing filters packed with a filter material such as a fiber material or porous material containing continuous pores has been widely used.
Removal of leukocytes using a leukocyte-removing filter includes the case where the leukocytes are removed from a whole blood product and the case where the leukocytes are removed from each blood component product that has been prepared. In the latter case, a filter is required for each blood component product. On the other hand, the former case is regarded to be more preferable, since leukocytes are removed from a whole blood product and the whole blood product from which the leukocytes have been removed is centrifuged to produce different and several kinds of blood component products not containing leukocytes.
Particularly, in recent years, a closed system prepared by integrating a bag for whole blood products, filters, bags for various blood component products that are obtained after centrifugal separation, and the like, to produce blood component products from which leukocytes have been aseptically removed has attracted attention and is used at blood centers and the like (Japanese Patent Application Laid-open No. 320064/1989, etc.).
In the method for preparing blood free from leukocytes using a filter such as a closed system commonly employed in blood centers and the like, a system in which bags for blood containing a large amount of leukocytes, a filter, and bags for collecting filtered blood, and the like are connected with each other via soft tubes made from vinyl chloride or the like may be used. More specifically, bags containing blood still containing un-removed leukocytes are hung on a rack with hooks and the like for a head drop of about 0.5–2 m, where the blood containing un-removed leukocytes is thoroughly mixed to homogenize. Thereafter, a clamp or a breakable seal in the tube is manually released to collect blood from which leukocytes have been removed in the recovery bag through a filter. The operation is substantially continuously conducted to minimize a burden on filtration operators.
A currently commercially available closed system for filtering a whole blood product removes leukocytes and plasma. Therefore, two blood component products from which leukocytes have been removed, a concentrated erythrocyte product and a plasma product, can be eventually obtained.
Since a whole blood product contains a large amount of leukocytes, a large capacity is required for the filter to remove leukocytes to the same degree as that achieved when removing leukocytes from each blood component product. However, an increase in the filter capacity results in an increase in the amount of blood that remains in the filter. Since the remaining blood is discarded together with the filter after filtration, an increased filter capacity has a problem of an increase in the loss of precious blood.
In addition, usually only a fresh whole blood product within three days at most and in many cases within several hours after collection is filtered for separation. Leukocytes removing capability of a filter is known to decrease when filtering a whole blood product that is very fresh and has a high temperature, in particular, within one hour after collection.
In view of these problems remaining still to be solved for efficiently removing leukocytes from a whole blood product, establishment of a blood filtering method that can remove leukocytes efficiently and at a high rate has been strongly desired.
In addition, a functional filter that can selectively remove only leukocytes from a whole blood product and recover platelets together with erythrocyte and plasma is being developed in recent years (Transfusion vol. 39 (1999), No. 10S, Supplement, S541-040K, S542-040K).
Three blood component products from which leukocytes have been removed, a concentrated leukocyte-free erythrocyte product, concentrated platelet product, and plasma product, can be eventually obtained by filtrating a whole blood product using such a filter. However, since platelets included in a fresh whole blood product are slightly activated due to a stress or the like during blood collection and are caused to easily to adhere to a filter, the technology cannot attain the level to ensure a high platelet recovery rate in a stable manner at the present time.
Japanese Patent No. 2521090 discloses a filter in which the filter material is maintained under wet conditions of saturated water content or more with an aqueous solution of a water-soluble substance harmless to water or living bodies. This technology reduces adhesion of platelets by wetting the filter material with an aqueous solution such as a physiological saline solution and increases the platelet recovery rate. However, according to investigations by the inventors of the present invention, a satisfactory increase in the platelet recovery rate was not achieved while maintaining high leukocyte removal capability. In addition, since the above disclosed filter is previously wetted with a physiological saline solution or the like, air that may be accidentally introduced in the filter not only can be discharged to outside the apparatus only with difficulty, but also may decrease or suspend the blood flow.
A method of fractionating a whole blood product into blood component products by centrifugation and filtering each blood component product is also known. For example, Japanese Patent Application Laid-open No. 2000-334034 discloses a method of subjecting a whole blood product to a very strong centrifugation of 3,520×g to separate the blood into three components, plasma, a buffy coat with a large platelet content, and concentrated erythrocytes, and sequentially filtering the buffy coat and concentrated erythrocytes using one filter. Two component blood products from which leukocytes have been removed, one a concentrated platelet product and the other a concentrated erythrocyte product, and a plasma product from which leukocytes have not been removed can be ultimately prepared using this method. However, according to investigations of the present inventors, such strong centrifugation activates platelets making it difficult to recover platelets at a satisfactory yield. In addition, the plasma product has a problem not to be removed leukocytes.
WO 92/07656 discloses a method and system of separating a whole blood obtained by blood collection into a concentrated erythrocyte product and platelet-rich plasma by weak centrifugation and filtering these separated fractions through different filters. Although leukocytes can be removed from all ultimately obtained blood component products according to the method, this method requires a complicated procedure of inserting two filters together with a plurality of bags into a centrifuge cup. In addition, use of two filters increases the cost.
A filter for selectively removing leukocytes from a whole blood product or a platelet product, such as platelet-rich plasma product or a concentrated platelet product prepared by a blood component collection apparatus, is commercially available and used in blood centers or clinical work front. Although some portion of platelets having high adhesion can be recovered by using this filter, the platelet recovery rate varies depending on individual difference of bloods and the like. Therefore, stability of the platelet recovery rate is still to be improved.
In this manner, there are many subjects to be improved in the existing technology for removing leukocytes from a whole blood product or the technology for recovering platelets from a whole blood product or a platelet product originating from a whole blood product or blood component collection while removing leukocytes. Development of a blood filtration method having an improved leukocytes removing capability so that a need for increasing filter capacity may not be required, exhibiting an increased recovery rate of platelets if the platelets are recovered, and being easily operated has been desired.
Since leukocytes removal has been recognized to be effective for safe transfusion, the amount of blood processed for removing leukocytes in blood centers and the like is increasing year by year. Automatic blood filtration has been desired to relieve burden loaded on operators processing a large amount of blood. Development to satisfy this requirement is ongoing.
Japanese Patent Application Laid-open No. 10-212237 discloses an apparatus for automatic filtration in which blood is filtered at a constant flow rate by using a pump. The apparatus maintains an appropriate flow rate of the filtered blood while monitoring pressure near the filter inlet port and controlling operation of the pump according to the pressure.
Japanese Patent Application Laid-open No. 09-108334 discloses an apparatus that can detect the fact that a predetermined amount of blood has been processed using a timer, a sensor to optically detect the blood surface or the gas/blood interface, a weight sensor to detect the amount of blood, a pressure sensor to detect the pressure of a tube, and the like, to automatically suspend filtration.
An automatic filtration apparatus in which not only is the blood filtration process automated, but also the blood filtration data (filtration time, temperature, flow rate, etc.) can be recoded by a computer has been developed to satisfy the requirements for quality control of blood products that has become more stringent than ever (Vox Sanguinis Vol. 78 (Supplement 1), 2000, P517, P518). An excellent feature of the apparatus is its capability of simultaneously automatically filtering 40 bloods while automatically homogenizing the bloods before or even during filtration by a mechanical means, and the capability of automatically recording filtration data, and the like.
The above automatic apparatuses have been developed with an objective of automatically filtering blood in a homogeneous state, automatically filtering at a constant flow rate of blood, and automatically suspending filtration operation. The blood filtration apparatus of the present invention is an automatic filtration initiate equipment suitable for implementing a blood filtration method for improving performance of the filter of the present invention and differs from the above-described automatic filtration apparatuses.
The features of the blood filtration method and automatic filtration apparatus of present invention will be described in more detail.